NRF2 Expression at T-All Diagnosis Could Predict Response to Induction Therapy

Background: The nuclear factor erythroid 2- related factor 2 (NRF2), has a significant impact on cancer chemoresistance. There is limited knowledge regarding its effect on the response of T cell acute lymphoblastic leukemia (T-ALL) to therapy. The objective of this study was to examine the effect of NRF2 expression on the induction remission response in T-ALL patients. Patients and Methods: This study involved 50 patients diagnosed with T-ALL and 20 controls subjects. The expression levels of NRF2 were assessed using real-time PCR at the time of diagnosis (day 0), on day 28 following induction chemotherapy, and in the control group. Results: The baseline expression levels of NRF2 in the T-ALL cohort at the time of diagnosis (day 0) [median 7.7 (range :6.8-10.2)] were markedly increased as compared to those observed in the T-ALL group on day 28 [(median:4.4 (range 3.2-9.1)], as well as in the normal control group [(median: 3.2 (range :2.7-4.9)] (P<0.0001 for all). A significant correlation was identified between NRF2 expression and BCL2 expression at the time of T-ALL diagnosis indicating that the expression of NRF2 is linked to the burden of blast cells in T-ALL. A high incidence of induction remission failure was noted among the subgroup of T-ALL patients exhibiting NRF2 overexpression. Furthermore, multivariate analysis indicated that increased NRF2 expression at diagnosis serves as an independent predictor (OR: 17.166 (2.587-31.901) of the induction remission failure. Conclusion, our research indicates that elevated NRF2 expression at the time of T-ALL diagnosis may serve as a predictor of inadequate response to induction chemotherapy, primarily due to the upregulation of BCL2 expression.